title: Mobilized adult pituitary stem cells contribute to endocrine regeneration in response to physiological demand.
abstract: Pituitary hormone deficiencies, with Growth Hormone deficiency being most frequent (1 in 3,500-10,000 births), cause significant morbidity. Regeneration of missing endocrine cells would be a significant improvement over hormone replacement therapies, which incur side effects and do not mimic physiological secretion patterns. Recent in vitro studies have identified a population of adult pituitary progenitors that express the HMG box transcription factors SOX2 and SOX9. Here, we apply cell-lineage tracing analysis to demonstrate that SOX2- and SOX9-expressing progenitors can self-renew and give rise to endocrine cells in vivo, suggesting that they are tissue stem cells. Moreover, we show that they can become mobilized and differentiate into the appropriate endocrine cell types in response to physiological stress. Our results highlight the pituitary as a model for exploring how physiological changes influence stem cell behavior and suggest that manipulation of endogenous pituitary stem cells is a potential therapeutic strategy for pituitary deficiencies.
authors.affiliation: Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, London NW7 1AA, UK. Electronic address: krizzot@nimr.mrc.ac.uk.
authors.forename: Karine
authors.initials: K
authors.lastname: Rizzoti
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Robin
authors.initials: R
authors.lastname: Lovell-Badge
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D055098:Endocrine Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000166:cytology* / Q000502:physiology*; D012038:Regeneration; D055758:SOX9 Transcription Factor / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism
chemical_list: D055758:SOX9 Transcription Factor; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C527933:Sox9 protein, mouse